1. Technical Field
The present invention relates to a method for producing L-cysteine, and a microorganism suitable for the production of L-cysteine. L-cysteine and derivatives thereof are used in the fields of pharmaceuticals, cosmetics, foods and the like.
2. Background Art
L-cysteine is conventionally obtained by extraction from keratin-containing substances such as hair, horns, and feathers, or by conversion of precursor DL-2-aminothiazoline-4-carboxylic acid using a microbial enzyme. Large scale production of L-cysteine has been attempted using an immobilized enzyme method with a novel enzyme.
Furthermore, production of L-cysteine has also been attempted by fermentation utilizing a microorganism. A method of producing L-cysteine using a microorganism has been reported, wherein said microorganism contains a DNA encoding serine acetyltransferase (SAT) with a mutation which prevents feedback inhibition by L-cysteine (WO 97/15673). A method of producing L-cysteine using a strain of Escherichia coli which contains a gene encoding SAT isozyme of Arabidopsis thaliana is disclosed in FEMS Microbiol. Lett., vol. 179 (1999) p 453-459. This SAT isozyme gene is resistant to feedback inhibition by L-cysteine. Also, a method of producing L-cysteine using a microorganism which overexpresses a gene encoding a protein that excretes an antibiotic or a toxic substance is disclosed in JP11-56381A.
Furthermore, the inventors of the present invention have disclosed a method of producing L-cysteine using a strain of Escherichia coli which contains serine acetyltransferase with reduced feedback inhibition by L-cysteine, and in which the L-cysteine-decomposing system is attenuated (JP11-155571A). The L-cysteine-decomposing system of the bacterium is attenuated by reduction of the intracellular activity of cysteine desulfhydrase (hereinafter, also referred to as “CD”).
Enzymes which have been reported to have CD activity in Escherichia coli include cystathionine-β-lyase (metC gene product, hereinafter, also referred to as “CBL”) (Chandra et. al., Biochemistry, vol. 21 (1982) p 3064-3069) and tryptophanase (tnaA gene product, hereinafter, also referred to as “TNase”) (Austin Newton, et al., J. Biol. Chem. vol. 240 (1965) p 1211-1218). A method of producing L-cysteine using an Escherichia coli strain which has reduced activities of cystathionine-(3-lyase and tryptophanase is disclosed in JP2003-169668A (EP1,298,200). However, no enzymes other than these have been previously reported to have CD activity.